Density-dependent regulation of cell-surface association of matrix metalloproteinase-2 (MMP-2) in breast-carcinoma cells.
Degradation of extracellular matrix takes place in areas of cell-matrix contacts and is partly carried out by the action of matrix metalloproteinases (MMP). MMP-2 is a member of the MMP family that has been associated with breast-cancer metastasis. In the present study, we investigated the association of MMP-2 to the surface of breast-cancer cells and revealed an MMP-2-binding site that is expressed on sparsely plated cells and which is progressively lost as the cells approach confluence. Gelatin zymography, immunostaining and flow cytometry of MDA-MB-231 cells from sparse cultures demonstrated binding both of latent and of activated exogenous MMP-2, while little or no binding of MMP-2 was observed in confluent culture. Analysis of the expression of MTI-MMP, TIMP-2 and alpha(v) integrin, 3 proteins shown to play a role in cell-surface association of MMP-2, revealed enhanced levels of these proteins in confluent MDA-MB-231 cells. Thus, the reduced MMP-2 binding to confluent cells is not related to a deficiency in these MMP-2-binding proteins. Taken together, these studies suggest that MMP-2 binding to the surface of breast-cancer cells is regulated by cell-cell interactions and that tumor cells invading from the main tumor mass can up-regulate their MMP-2-binding capacity to acquire greater invasive capacity.
Menashi
S
S
Unité 353 INSERM, Hôpital Saint-Louis, Paris, France. s.menashi@chu-stlouis.fr
Dehem
M
M
Souliac
I
I
Legrand
Y
Y
Fridman
R
R
D015703:Antigens, CD / Q000032:analysis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002452:Cell Count; D005260:Female; D005434:Flow Cytometry; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D039564:Integrin alphaV; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D039564:Integrin alphaV; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2